Loesch J, Siegers C P, Younes M
Department of Toxicology, Medical University of Lübeck, Federal Republic of Germany.
Pharmacol Res Commun. 1987 Jun;19(6):395-403. doi: 10.1016/0031-6989(87)90079-8.
The metabolism of halothane and methoxyflurane was measured in vitro by the vial equilibration method using the S-9-fraction from rat liver as source of enzymes. Kinetic values were measured for halothane: Vmax = 11.6 nmol/g.min, KM = 19.6 mumol/l and methoxyflurane: Vmax = 12.0 nmol/g.min, KM = 17.5 mumol/l. Dithiocarb showed strong inhibitory activity on halothane and methoxyflurane metabolism; inhibition constants were calculated as Ki = 0.051 mmol/l and Ki = 0.004 mmol/l, respectively. Cimetidine inhibited the metabolism of both anesthetics to a lesser extent. Inhibition constants were calculated as Ki = 16.2 mmol/l and Ki = 8.2 mmol/l for halothane and methoxyflurane, respectively. The observed inhibitory properties of dithiocarb and cimetidine on the metabolism of halothane and methoxyflurane may be of interest in connection with the problem of toxic liver and kidney injury after anesthesia with these agents.
采用大鼠肝脏S-9组分作为酶源，通过小瓶平衡法在体外测定了氟烷和甲氧氟烷的代谢情况。测定了氟烷的动力学值：Vmax = 11.6 nmol/g·min，KM = 19.6 μmol/L；以及甲氧氟烷的动力学值：Vmax = 12.0 nmol/g·min，KM = 17.5 μmol/L。二硫代碳对氟烷和甲氧氟烷的代谢表现出强烈的抑制活性；计算出的抑制常数分别为Ki = 0.051 mmol/L和Ki = 0.004 mmol/L。西咪替丁对两种麻醉剂代谢的抑制作用较小。计算出氟烷和甲氧氟烷的抑制常数分别为Ki = 16.2 mmol/L和Ki = 8.2 mmol/L。二硫代碳和西咪替丁对氟烷和甲氧氟烷代谢的抑制特性，可能与使用这些药物麻醉后出现的肝毒性和肾毒性问题有关。
